Angiogenesis (the grow or assembly or formation of blood vessels) is an essential process during embryogenesis and pre-adult physiological development. In adults, angiogenesis is an important beneficial reparative process in wound healing, menstrual cycle, and bone repair, as well as in the recovery from stroke, peptic ulcers and certain cardiovascular diseases. Preservation of healthy network of dermal blood vessels is also essential for skin health and delaying skin ageing process. Several endogenous angiogenesis stimulators or factors have been reported that include basic fibroblast growth factor (bFGF) and its fragments, vascular endothelial growth factors (VEGF) and their fragments, interleukin 1 alpha and others. Therapeutic administration of some of these factors has been described to be useful and beneficial in many of the aforementioned physiological conditions. For example, basic fibroblast growth factor (bFGF) has been reported to improve quality of life as assessed by Seattle Angina Questionnaire and improve exercise tolerance as assessed by treadmill exercise testing in patients ischemic heart disease not amenable to treatment with coronary artery bypass graft (CABG) or percutaneous transluminal coronary angioplasty (PTCA) (Laham et al., 2000). Moreover, bFGF was shown by magnetic resonance imaging (MRI) to increase regional wall thickening and to reduce the extent of the ischemic area at all time points compared with baseline. However, effective angiogenesis stimulators with low side effect still represent a therapeutic gap even today, since there are no angiogenesis stimulators available that are approved by FDA for broad human use.
Furthermore, conditions, such as wounds, photodamaged and aged skin require activation of proliferation of several cell types, including endothelial cells and fibroblasts.
In our invention, we teach that an aqueous extract from Angelica sinensis or a fraction or a lyophilizate thereof, or one or more active components contained in said extract, stimulates endothelial cell growth in vitro, vessel-like structure formation in vitro and angiogenesis in vivo, indicating that Angelica sinensis or the compositions thereof may be useful for treating a vast array of pathologic conditions which require stimulation of angiogenesis, such as cardiovascular diseases, stroke, bone loss, peptic ulcers and skin wounds. It also indicates that SBD.4 may delay the process of dermal ageing by maintaining healthy irrigation of the skin and find use in the cosmetic products as active ingredients.
Furthermore, we teach that SBD.4 stimulates the proliferation of dermal fibroblasts. Proliferation of dermal fibroblasts is necessary for wound closure. Several angiostimulators were shown to enhance fibroblast growth (e.g. bFGF). Fibroblast cells are the major component of the dermis layer of the skin. They secrete collagens and other extracellular matrix components, which determine the elasticity, thickness and resilience of the skin. Therefore, natural products, which can support fibroblast metabolism and survival, but which at least minimally stimulate cancer cells, are of major interest as, for example, wound healing and cosmetic active ingredients.
Furthermore, we teach that SBD.4 not only protects and enhances microcirculation and dermal fibroblast growth, but also stimulates collagen I levels in fibroblast culture medium. Collagen I is a key component of extracellular matrix in the skin. In aged and damaged skin, collagen I levels are decreased due to the lower amount and quality of dermal fibroblasts. Collagen I output is also an important part of the wound healing process.